Biomedical Engineering Reference
In-Depth Information
types,. but. by. imaging. repeatedly. over. time,. this. group 49 . detected. the. onset. in. the. Vx-2.
tumors.of.the.angiogenic.switch 50,51 —the.point.when.the.tumor.transitions.into.the.angio-
genic.phenotype,.becoming.more.aggressive.and.prone.to.metastasis.
This. is. an. excellent. example. of. noninvasive. phenotyping. through. molecular. imaging.
using. a. single. biomarker.. Of. course,. this. could. be. extended. to. use. a. cocktail. of. agents.
targeted.to.a.variety.of.biomarkers..If.each.uniquely.targeted.agent.had.a.distinguishable.
signature. (i.e.,. a. unique. spectrum. on. magnetic. resonance),. then. multiparametric. imag-
ing.could.be.performed.to.characterize.disease.more.completely. 52 .Caruthers.et.al..dem-
onstrated.the.potential.of.this.using.multiple.perluorocarbon.nanoparticles,.each.with.a.
unique.signature.(e.g.,.color).on.MRI,.in.both.in.vitro 34 .and.in.vivo 53 .experiments.
Early. diagnosis. and. speciic. characterization. of. disease. through. biomarkers. such. as.
angiogenesis.in.cancer.have.great.utility..Phenotyping.the.disease.helps.guide.the.selec-
tion.of.effective.therapy..Importantly,.it.can.help.avoid.applying.the.wrong.therapy,.thereby.
saving.the.patient.the.high.costs.associated.with.ineffective.therapy,.namely,.exposure.to.
potentially.harmful.side.effects.and.lost.time.getting.to.the.successful.therapy.regimen.
4.5 TargetedDrugDelivery
While. early,. accurate. diagnosis. with. quantitative. characterization. of. disease. could. have.
considerable.clinical.relevance,.this.information.has.far.greater.impact.if.it.helps.guide.and.
monitor.earlier,.more.effective.therapies..Nanoparticles.designed.for.site-targeted.molecu-
lar. imaging. can. also. be. designed. to. be. multifunctional,. incorporating. therapeutics. for.
targeted.delivery.
Nanotechnology.has.much.to.offer.in.the.(re)development.of.drugs,.drug.delivery,.and.
pharmacokinetic. control. 54 . From. transdermal. systems. to. controlled-release. approaches,.
there.is.a.vast.array.of.activity.in.this.ield. 24,55-69 .One.example.is.the.liquid.perluorocar-
bon.nanoparticles.presented.above..The.method.employed.is.not.based.on.slow.release.or.
targeted.cell.uptake.of.the.particle,.but.rather.on.a.process.labeled.contact.facilitated.drug.
delivery 70 .(Figure 4.2).
These. therapeutic. nanoparticles. are. manufactured. with. lipophilic. drugs. incorporated.
into.their.outer.lipid.monolayer..The.drugs.do.not.dissolve.into.the.perluorocarbon.core.
and,.due.to.lipophilicity,.do.not.readily.diffuse.into.the.aqueous.surrounding.(i.e.,.blood.
serum).. The. drug. is. trapped. at. the. nanoparticle. surface. in. high. concentration,. but. with.
no. release,. and. therefore. no. effect.. If. the. nanoparticle. binds. to. the. targeted. cell. surface.
receptor.and.remains.in.close.proximity.for.an.extended.time,.there.is.an.opportunity.for.
interaction.between.the.two.lipid.membranes..Through.these.direct.interactions,.the.lipo-
philic.drug.can.exchange.from.the.nanoparticle.membrane.to.the.targeted.cell.membrane,.
later.to.be.internalized.by.the.cell's.normal.processes 71,72 .(Figure 4.3)..This.exchange.does.
not.require.cell.disruption.or.particle.internalization,.but.it.can.be.augmented.by.adding.
energy. through. various. techniques,. such. as. ultrasound. 73 . However,. without. the. direct.
contact.afforded.by.ligand-directed.binding,.no.drug.is.released.and.therapeutic.effect.is.
not.induced. 71,74 .As.a.result,.high.concentrations.of.drug.can.be.accumulated.at.the.site.of.
interest,.though.the.blood.serum.level.of.the.drug.is.effectively.zero.(thereby.drastically.
reducing.systemic.side.effects).
Antiangiogenic.therapy.can.be.delivered.with.the.same.agents.used.in.targeted.imag-
ing. of. angiogenesis.. Packaging. a. potent. antiangiogenic. compound. fumagillin, 75 . the.
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